AUTOCRINE REGULATION OF MACROPHAGE DIFFERENTIATION AND 92-KDA GELATINASE PRODUCTION BY TUMOR-NECROSIS-FACTOR-ALPHA VIA ALPHA(5)BETA(1) INTEGRIN IN HL-60 CELLS

Citation
B. Xie et al., AUTOCRINE REGULATION OF MACROPHAGE DIFFERENTIATION AND 92-KDA GELATINASE PRODUCTION BY TUMOR-NECROSIS-FACTOR-ALPHA VIA ALPHA(5)BETA(1) INTEGRIN IN HL-60 CELLS, The Journal of biological chemistry, 273(19), 1998, pp. 11583-11588
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
19
Year of publication
1998
Pages
11583 - 11588
Database
ISI
SICI code
0021-9258(1998)273:19<11583:AROMDA>2.0.ZU;2-L
Abstract
Tumor necrosis factor-alpha (TNF-alpha) gene is one of the early respo nse genes induced by phorbol la-myristate 13-acetate (PMA) in human HL -60 myeloid leukemia cells. In the present study, we examined the role of the TNF-alpha autocrine loop in PMA-induced macrophage differentia tion and gene expression of 92- and 72-kDa gelatinases (MMP-9 and MMP- 2). In HL-60 cells, PMA inhibited cell proliferation and induced cell adhesion and spreading, expression of surface maturation marker OKM1 a nd phagocytic activity, as well as the expression of both gelatinases, which all characterize the macrophage phenotype. In contrast, TNF-alp ha alone was only effective in inhibiting cell proliferation. Blocking the endogenous TNF-alpha activity with neutralizing anti-TNF-alpha an tibodies abolished all these PMA-induced events with the exception of MMP-2 gene expression. Since fibronectin (FN)-mediated cell adhesion a nd spreading are prerequisite for both macrophage differentiation and MMP-9 gene expression in HL-60 cells, we hypothesized that TNF-alpha m ight be involved in modulating the expression of either the FN or its integrin receptor genes. Whereas PMA substantially enhanced the steady state mRNA and protein levels of both FN and alpha(5) beta(1) integri ns, TNF-alpha alone had little effect on the expression of these genes . However, anti-TNF-alpha antibodies blocked PMA-induced augmentation of both alpha(5) and beta(1) integrin gene expression without affectin g the expression of the FN gene. Our results suggest that TNF-alpha ma y regulate macrophage differentiation and critical matrix-degrading ac tivities of myeloid progenitor cells in an autocrine manner by augment ing surface levels of the alpha(5) beta(1) integrin, thus promoting in teractions with the extracellular matrix, a key event for maturation a nd migration of these cells during inflammation.